Homologous recombination and, more specifically D-loop mediated recombination, provide a method for genetically modifying chromosomal DNA sequences in a precise way. In addition to the possibility of introducing small precise mutations in order to alter the activity of the chromosomal DNA sequences, such a methodology makes it possible to correct the genetic defects in genes which can cause disease. Unfortunately, current methods for achieving homologous recombination are inherently inefficient, in that homologous recombination or D-loop recombination-mediated gene repair can usually be achieved in only a small proportion of cells that have taken up the relevant “targeting or correcting” DNA. For example, in cultured mammalian cells, such recombinational events usually occur in only one in ten thousand cells which have taken up the relevant targeting or correcting DNA. Accordingly, the use of biochemical selections are normally necessary to identify and isolate cells which have successfully recombined input DNA.
Thus, there is a need to develop new and improved methods of homologous recombination or D-loop recombination-mediated gene repair.